Fertility, pregnancy and lactation in women with systemic lupus erythematosus

Fertility, pregnancy and lactation in women with systemic lupus erythematosus

  • Nguyen, N. V. et al. Nationwide temporal trends in adverse pregnancy outcomes and treatments in systemic lupus erythematosus pregnancy over two decades in Sweden. Arthritis Rheumatol. https://doi.org/10.1002/art.70018 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Abheiden, C. N. H. et al. Systemic lupus erythematosus is associated with an increased frequency of spontaneous preterm births: systematic review and meta-analysis. Am. J. Obstet. Gynecol. 231, 408–416.e21 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Wind, M. et al. Pregnancy outcome predictors in systemic lupus erythematosus: a systematic review and meta-analysis. Lancet Rheumatol. 6, e667–e683 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kroese, S. J. et al. Maternal and perinatal outcome in women with systemic lupus erythematosus: a retrospective bicenter cohort study. J. Immunol. Res. 2017, 8245879 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Eudy, A. M. et al. Effect of pregnancy on disease flares in patients with systemic lupus erythematosus. Ann. Rheum. Dis. 77, 855–860 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jolving, L. R. et al. Prevalence of maternal chronic diseases during pregnancy — a nationwide population based study from 1989 to 2013. Acta Obstet. Gynecol. Scand. 95, 1295–1304 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Skomsvoll, J. F., Ostensen, M., Baste, V. & Irgens, L. M. Number of births, interpregnancy interval, and subsequent pregnancy rate after a diagnosis of inflammatory rheumatic disease in Norwegian women. J. Rheumatol. 28, 2310–2314 (2001).

    CAS 
    PubMed 

    Google Scholar
     

  • Vinet, E. et al. A population-based assessment of live births in women with systemic lupus erythematosus. Ann. Rheum. Dis. 71, 557–559 (2012).

    Article 
    PubMed 

    Google Scholar
     

  • Vinet, E. et al. Decreased live births in women with systemic lupus erythematosus. Arthritis Care Res. 63, 1068–1072 (2011).

    Article 

    Google Scholar
     

  • Kerola, A. M. et al. Patterns of reproductive health in inflammatory rheumatic diseases and other immune-mediated diseases: a nationwide registry study. Rheumatology 63, 2701–2710 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Clowse, M. E., Chakravarty, E., Costenbader, K. H., Chambers, C. & Michaud, K. Effects of infertility, pregnancy loss, and patient concerns on family size of women with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res. 64, 668–674 (2012).

    Article 

    Google Scholar
     

  • Andreoli, L. et al. “Disease knowledge index” and perspectives on reproductive issues: a nationwide study on 398 women with autoimmune rheumatic diseases. Joint Bone Spine 86, 475–481 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Xia, X. Y. et al. Current investigation of the high prevalence of sexual dysfunction in female patients with systemic lupus erythematosus: a cross-sectional study. Rheumatol. Int. 44, 2147–2157 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Phuti, A., Hodkinson, B., Tikly, M. & Schneider, M. ‘The feeling of not being entitled to something’: fertility, pregnancy, and sexuality among women with systemic lupus erythematosus in South Africa. Scand. J. Rheumatol. 49, 214–220 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hickman, R. A. & Gordon, C. Causes and management of infertility in systemic lupus erythematosus. Rheumatology 50, 1551–1558 (2011).

    Article 
    PubMed 

    Google Scholar
     

  • Krasselt, M. & Baerwald, C. Sex, symptom severity, and quality of life in rheumatology. Clin. Rev. Allergy Immunol. 56, 346–361 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Perez-Garcia, L. F. et al. Sexual function and reproduction can be impaired in men with rheumatic diseases: a systematic review. Semin. Arthritis Rheum. 50, 557–573 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Blomjous, B. S. et al. Desire to have children and preferences regarding to pre-pregnancy counselling in women with SLE. Rheumatology 60, 2706–2713 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Flint, J. et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-part II: analgesics and other drugs used in. Rheumatology 55, 1698–1702 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Flint, J. et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology 55, 1693–1697 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Russell, M. D. et al. British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory anti-rheumatic drugs and corticosteroids. Rheumatology 62, e48–e88 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Andreoli, L. et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann. Rheum. Dis. 76, 476–485 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sammaritano, L. R. et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Care Res. 72, 461–488 (2020).

    Article 

    Google Scholar
     

  • Ruegg, L. et al. EULAR recommendations for use of antirheumatic drugs in reproduction, pregnancy, and lactation: 2024 update. Ann. Rheum. Dis. 84, 910–926 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Luo, W., Mao, P., Zhang, L., Chen, X. & Yang, Z. Assessment of ovarian reserve by serum anti-Mullerian hormone in patients with systemic lupus erythematosus: a meta-analysis. Ann. Palliat. Med. 9, 207–215 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Silva, C. A. & Brunner, H. I. Gonadal functioning and preservation of reproductive fitness with juvenile systemic lupus erythematosus. Lupus 16, 593–599 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Shabanova, S. S., Ananieva, L. P., Alekberova, Z. S. & Guzov, I. I. Ovarian function and disease activity in patients with systemic lupus erythematosus. Clin. Exp. Rheumatol. 26, 436–441 (2008).

    CAS 
    PubMed 

    Google Scholar
     

  • Aringer, M. & Smolen, J. S. Safety of off-label biologicals in systemic lupus erythematosus. Expert. Opin. Drug. Saf. 14, 243–251 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Clowse, M. E., Magder, L. S., Witter, F. & Petri, M. The impact of increased lupus activity on obstetric outcomes. Arthritis Rheum. 52, 514–521 (2005).

    Article 
    PubMed 

    Google Scholar
     

  • Boumpas, D. T. et al. Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. Ann. Intern. Med. 119, 366–369 (1993).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Houssiau, F. A. et al. The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Ann. Rheum. Dis. 69, 61–64 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tamirou, F. et al. Brief report: the Euro-Lupus low-dose intravenous cyclophosphamide regimen does not impact the ovarian reserve, as measured by serum levels of anti-mullerian hormone. Arthritis Rheumatol. 69, 1267–1271 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • McInerney, K. A. et al. Preconception use of pain-relievers and time-to-pregnancy: a prospective cohort study. Hum. Reprod. 32, 103–111 (2017).

    CAS 
    PubMed 

    Google Scholar
     

  • Guballa, N., Sammaritano, L., Schwartzman, S., Buyon, J. & Lockshin, M. D. Ovulation induction and in vitro fertilization in systemic lupus erythematosus and antiphospholipid syndrome. Arthritis Rheum. 43, 550–556 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ragab, A., Barakat, R., Ragheb, M., State, O. & Badawy, A. Subfertility treatment in women with systemic lupus erythematosus. J. Obstet. Gynaecol. 32, 569–571 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Roman, A., Ramirez, A. & Fox, N. S. Prevention of preterm birth in twin pregnancies. Am. J. Obstet. Gynecol. MFM 4, 100551 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Bellver, J. & Pellicer, A. Ovarian stimulation for ovulation induction and in vitro fertilization in patients with systemic lupus erythematosus and antiphospholipid syndrome. Fertil. Steril. 92, 1803–1810 (2009).

    Article 
    PubMed 

    Google Scholar
     

  • Orquevaux, P. et al. In vitro fertilization in 37 women with systemic lupus erythematosus or antiphospholipid syndrome: a series of 97 procedures. J. Rheumatol. 44, 613–618 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Reggia, R. et al. An observational multicentre study on the efficacy and safety of assisted reproductive technologies in women with rheumatic diseases. Rheumatol. Adv. Pract. 3, rkz005 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lao, M. et al. Pregnancy outcomes in patients receiving assisted reproductive therapy with systemic lupus erythematosus: a multi-center retrospective study. Arthritis Res. Ther. 25, 13 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Andersson, K. The levonorgestrel intrauterine system: more than a contraceptive. Eur. J. Contracept. Reprod. Health Care 6, 15–22 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tepper, N. K., Whiteman, M. K., Marchbanks, P. A., James, A. H. & Curtis, K. M. Progestin-only contraception and thromboembolism: a systematic review. Contraception 94, 678–700 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rojas-Villarraga, A., Torres-Gonzalez, J. V. & Ruiz-Sternberg, A. M. Safety of hormonal replacement therapy and oral contraceptives in systemic lupus erythematosus: a systematic review and meta-analysis. PLoS ONE 9, e104303 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Teal, S. & Edelman, A. Contraception selection, effectiveness, and adverse effects: a review. JAMA 326, 2507–2518 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Petri, M. et al. Combined oral contraceptives in women with systemic lupus erythematosus. N. Engl. J. Med. 353, 2550–2558 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cockrum, R. H., Soo, J., Ham, S. A., Cohen, K. S. & Snow, S. G. Association of progestogens and venous thromboembolism among women of reproductive age. Obstet. Gynecol. 140, 477–487 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Buyon, J. P., Kim, M. Y. & Salmon, J. E. Predictors of pregnancy outcomes in patients with lupus. Ann. Intern. Med. 164, 131 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Andreoli, L. et al. Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study. RMD Open. https://doi.org/10.1136/rmdopen-2024-004091 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Smyth, A. et al. A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis. Clin. J. Am. Soc. Nephrol. 5, 2060–2068 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lateef, A. & Petri, M. Managing lupus patients during pregnancy. Best. Pract. Res. Clin. Rheumatol. 27, 435–447 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Clowse, M. E., Magder, L., Witter, F. & Petri, M. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum. 54, 3640–3647 (2006).

    Article 
    PubMed 

    Google Scholar
     

  • Tani, C. et al. Are remission and low disease activity state ideal targets for pregnancy planning in systemic lupus erythematosus? A multicentre study. Rheumatology 60, 5610–5619 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Bobrie, G., Liote, F., Houillier, P., Grunfeld, J. P. & Jungers, P. Pregnancy in lupus nephritis and related disorders. Am. J. Kidney Dis. 9, 339–343 (1987).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hayslett, J. P. Maternal and fetal complications in pregnant women with systemic lupus erythematosus. Am. J. Kidney Dis. 17, 123–126 (1991).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Larosa, M. et al. Evaluation of lupus anticoagulant, damage, and remission as predictors of pregnancy complications in systemic lupus erythematosus: the French GR2 study. Rheumatology 61, 3657–3666 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saavedra, M. A. et al. Impact of previous lupus nephritis on maternal and fetal outcomes during pregnancy. Clin. Rheumatol. 31, 813–819 (2012).

    Article 
    PubMed 

    Google Scholar
     

  • Chen, Y. et al. Good pregnancy outcomes in lupus nephritis patients with complete renal remission. Nephrol. Dial. Transpl. 37, 1888–1894 (2022).

    Article 

    Google Scholar
     

  • Buyon, J. P., Tamerius, J., Ordorica, S., Young, B. & Abramson, S. B. Activation of the alternative complement pathway accompanies disease flares in systemic lupus erythematosus during pregnancy. Arthritis Rheum. 35, 55–61 (1992).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yang, Y. et al. Risk and protective factors of disease flare during pregnancy in systemic lupus erythematosus: a systematic review and meta-analysis. Clin. Rheumatol. 44, 887–899 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Saavedra, M. A. et al. Primigravida is associated with flare in women with systemic lupus erythematosus. Lupus 24, 180–185 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mehta, B. et al. Trends in maternal and fetal outcomes among pregnant women with systemic lupus erythematosus in the United States: a cross-sectional analysis. Ann. Intern. Med. 171, 164–171 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Simard, J. F. et al. Maternal hypertensive disorders in pregnant women with systemic lupus erythematosus and future cardiovascular outcomes. Arthritis Care Res. 73, 574–579 (2021).

    Article 

    Google Scholar
     

  • Liu, T., Xu, Y., Gong, Y., Zheng, J. & Chen, Z. The global burden of disease attributable to preterm birth and low birth weight in 204 countries and territories from 1990 to 2019: an analysis of the Global Burden of Disease Sstudy. J. Glob. Health 14, 04109 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Clowse, M. E., Jamison, M., Myers, E. & James, A. H. A national study of the complications of lupus in pregnancy. Am. J. Obstet. Gynecol. 199, 127.E1–127.E6 (2008).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yasmeen, S., Wilkins, E. E., Field, N. T., Sheikh, R. A. & Gilbert, W. M. Pregnancy outcomes in women with systemic lupus erythematosus. J. Matern. Fetal Med. 10, 91–96 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Clark, C. A., Spitzer, K. A. & Laskin, C. A. Decrease in pregnancy loss rates in patients with systemic lupus erythematosus over a 40-year period. J. Rheumatol. 32, 1709–1712 (2005).

    PubMed 

    Google Scholar
     

  • Petri, M., Daly, R. P. & Pushparajah, D. S. Healthcare costs of pregnancy in systemic lupus erythematosus: retrospective observational analysis from a US health claims database. J. Med. Econ. 18, 967–973 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bramham, K. et al. Pregnancy outcomes in systemic lupus erythematosus with and without previous nephritis. J. Rheumatol. 38, 1906–1913 (2011).

    Article 
    PubMed 

    Google Scholar
     

  • Ko, H. S. et al. Pregnancy outcomes and appropriate timing of pregnancy in 183 pregnancies in Korean patients with SLE. Int. J. Med. Sci. 8, 577–583 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ateka-Barrutia, O. & Khamashta, M. A. The challenge of pregnancy for patients with SLE. Lupus 22, 1295–1308 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mankee, A., Petri, M. & Magder, L. S. Lupus anticoagulant, disease activity and low complement in the first trimester are predictive of pregnancy loss. Lupus Sci. Med. 2, e000095 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Abheiden, C. N. et al. Low-molecular-weight heparin and aspirin use in relation to pregnancy outcome in women with systemic lupus erythematosus and antiphospholipid syndrome: a cohort study. Hypertens. Pregnancy 36, 8–15 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • McMillan, E. et al. Management of pregnancy in women with pulmonary hypertension secondary to SLE and anti-phospholipid syndrome. Lupus 11, 392–398 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, X. et al. The conditions that patients with systemic lupus erythematosus should fulfill before pregnancy to optimize outcomes: a large-scale multicenter cohort study from China. Arthritis Res. Ther. 27, 31 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kaplowitz, E. T. et al. Contribution of socioeconomic status to racial/ethnic disparities in adverse pregnancy outcomes among women with systemic lupus erythematosus. Arthritis Care Res. 70, 230–235 (2018).

    Article 
    CAS 

    Google Scholar
     

  • Clowse, M. E. B. et al. Implications of the accuracy of diagnostic algorithms for systemic lupus on our understanding of racial disparities in pregnancy outcomes. Rheumatology 63, 119–126 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Clowse, M. E., Magder, L. S. & Petri, M. The clinical utility of measuring complement and anti-dsDNA antibodies during pregnancy in patients with systemic lupus erythematosus. J. Rheumatol. 38, 1012–1016 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Clowse, M. E., Magder, L. S., Witter, F. & Petri, M. Early risk factors for pregnancy loss in lupus. Obstet. Gynecol. 107, 293–299 (2006).

    Article 
    PubMed 

    Google Scholar
     

  • Radin, M. et al. Complement levels during the first trimester predict disease flare and adverse pregnancy outcomes in systemic lupus erythematosus: a network meta-analysis on 532 pregnancies. Autoimmun. Rev. 22, 103467 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Abalos, E., Cuesta, C., Grosso, A. L., Chou, D. & Say, L. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur. J. Obstet. Gynecol. Reprod. Biol. 170, 1–7 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • He, W. R. & Wei, H. Maternal and fetal complications associated with systemic lupus erythematosus: an updated meta-analysis of the most recent studies (2017-2019). Medicine 99, e19797 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tani, C. et al. Impact of low-dose acetylsalicylic acid on pregnancy outcome in systemic lupus erythematosus: results from a multicentre study. Lupus Sci. Med. https://doi.org/10.1136/lupus-2022-000714 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gordijn, S. J. et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet. Gynecol. 48, 333–339 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chakravarty, E. F., Nelson, L. & Krishnan, E. Obstetric hospitalizations in the United States for women with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 54, 899–907 (2006).

    Article 
    PubMed 

    Google Scholar
     

  • Mok, M. Y. et al. Clinical predictors of fetal and maternal outcome in Chinese patients with systemic lupus erythematosus. Ann. Rheum. Dis. 63, 1705–1706 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Abou-Nassar, K., Carrier, M., Ramsay, T. & Rodger, M. A. The association between antiphospholipid antibodies and placenta mediated complications: a systematic review and meta-analysis. Thromb. Res. 128, 77–85 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Canti, V. et al. Low incidence of intrauterine growth restriction in pregnant patients with systemic lupus erythematosus taking hydroxychloroquine. Immunol. Med. 44, 204–210 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kim, S. Y. & Lee, J. H. Prognosis of neonates in pregnant women with systemic lupus erythematosus. Yonsei Med. J. 49, 515–520 (2008).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wei, S., Lai, K., Yang, Z. & Zeng, K. Systemic lupus erythematosus and risk of preterm birth: a systematic review and meta-analysis of observational studies. Lupus 26, 563–571 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chakravarty, E. F. et al. Factors that predict prematurity and preeclampsia in pregnancies that are complicated by systemic lupus erythematosus. Am. J. Obstet. Gynecol. 192, 1897–1904 (2005).

    Article 
    PubMed 

    Google Scholar
     

  • Kaizer, A. M. et al. Reducing the burden of surveillance in pregnant women with no history of fetal atrioventricular block using the negative predictive value of anti-Ro/SSA antibody titers. Am. J. Obstet. Gynecol. 227, 761.e1–761.e10 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brucato, A. et al. Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis: a prospective study of 100 women. Arthritis Rheum. 44, 1832–1835 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Llanos, C. et al. Recurrence rates of cardiac manifestations associated with neonatal lupus and maternal/fetal risk factors. Arthritis Rheum. 60, 3091–3097 (2009).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Buyon, J. P. et al. Prospective evaluation of high titer autoantibodies and fetal home monitoring in the detection of atrioventricular block among anti-SSA/Ro pregnancies. Arthritis Rheumatol. 76, 411–420 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fredi, M. et al. First report of the Italian registry on immune-mediated congenital heart block (Lu.Ne Registry). Front. Cardiovasc. Med. 6, 11 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Izmirly, P. M. et al. Maternal and fetal factors associated with mortality and morbidity in a multi-racial/ethnic registry of anti-SSA/Ro-associated cardiac neonatal lupus. Circulation 124, 1927–1935 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Moak, J. P. et al. Congenital heart block: development of late-onset cardiomyopathy, a previously underappreciated sequela. J. Am. Coll. Cardiol. 37, 238–242 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Izmirly, P. et al. Hydroxychloroquine to prevent recurrent congenital heart block in fetuses of anti-SSA/Ro-positive mothers. J. Am. Coll. Cardiol. 76, 292–302 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zuppa, A. A. et al. Neonatal lupus: follow-up in infants with anti-SSA/Ro antibodies and review of the literature. Autoimmun. Rev. 16, 427–432 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • van Baar, P. M., Welters, S. M., Ravelli, A. C. J., de Boer, M. A. & de Groot, C. J. M. Cardiovascular mortality risk a decade after twin and singleton pregnancies complicated by hypertensive disorders of pregnancy. Pregnancy Hypertens. 28, 9–14 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Forger, F. & Villiger, P. M. Immunological adaptations in pregnancy that modulate rheumatoid arthritis disease activity. Nat. Rev. Rheumatol. 16, 113–122 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Ander, S. E., Diamond, M. S. & Coyne, C. B. Immune responses at the maternal-fetal interface. Sci. Immunol. 4, eaat6114 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Orefice, R. Immunology and the immunological response in pregnancy. Best. Pract. Res. Clin. Obstet. Gynaecol. 76, 3–12 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tsokos, G. C. The immunology of systemic lupus erythematosus. Nat. Immunol. 25, 1332–1343 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Girardi, G. et al. Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. J. Clin. Invest. 112, 1644–1654 (2003).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yalavarthi, S. et al. Release of neutrophil extracellular traps by neutrophils stimulated with antiphospholipid antibodies: a newly identified mechanism of thrombosis in the antiphospholipid syndrome. Arthritis Rheumatol. 67, 2990–3003 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jiang, M. et al. The enrichment of neutrophil extracellular traps impair the placentas of systemic lupus erythematosus through accumulating decidual NK cells. Sci. Rep. 11, 6870 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Redecha, P. et al. Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury. Blood 110, 2423–2431 (2007).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Matrai, C. E., Rand, J. H. & Baergen, R. N. Absence of distinct immunohistochemical distribution of annexin A5, C3b, C4d, and C5b-9 in placentas from patients with antiphospholipid antibodies, preeclampsia, and systemic lupus erythematosus. Pediatr. Dev. Pathol. 22, 431–439 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Marder, W. et al. Placental histology and neutrophil extracellular traps in lupus and pre-eclampsia pregnancies. Lupus Sci. Med. 3, e000134 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grennan, D. M., McCormick, J. N., Wojtacha, D., Carty, M. & Behan, W. Immunological studies of the placenta in systemic lupus erythematosus. Ann. Rheum. Dis. 37, 129–134 (1978).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shamonki, J. M., Salmon, J. E., Hyjek, E. & Baergen, R. N. Excessive complement activation is associated with placental injury in patients with antiphospholipid antibodies. Am. J. Obstet. Gynecol. 196, 167.e1–167.e5 (2007).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Medina, G. et al. The prognostic value of neutrophile/lymphocyte ratio and serum chemerin to predict maternal-fetal complications in pregnant systemic lupus erythematosus patients. Lupus 32, 1409–1417 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sahin, R. et al. The role of first-trimester NLR (neutrophil to lymphocyte ratio), systemic immune-inflammation index (SII), and, systemic immune-response index (SIRI) in the prediction of composite adverse outcomes in pregnant women with systemic lupus erythematosus. J. Reprod. Immunol. 158, 103978 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Stockfelt, M. et al. Activated low-density granulocytes in peripheral and intervillous blood and neutrophil inflammation in placentas from SLE pregnancies. Lupus Sci. Med. https://doi.org/10.1136/lupus-2020-000463 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Torell, A. et al. Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus. Arthritis Res. Ther. 25, 107 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Girardi, G., Yarilin, D., Thurman, J. M., Holers, V. M. & Salmon, J. E. Complement activation induces dysregulation of angiogenic factors and causes fetal rejection and growth restriction. J. Exp. Med. 203, 2165–2175 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hong, S. et al. Longitudinal profiling of human blood transcriptome in healthy and lupus pregnancy. J. Exp. Med. 216, 1154–1169 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ding, X. et al. RSAD2: a pathogenic interferon-stimulated gene at the maternal-fetal interface of patients with systemic lupus erythematosus. Cell Rep. Med. 6, 101974 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Buchrieser, J. et al. IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise. Science 365, 176–180 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hellwig, K., Duarte Caron, F., Wicklein, E. M., Bhatti, A. & Adamo, A. Pregnancy outcomes from the global pharmacovigilance database on interferon beta-1b exposure. Ther. Adv. Neurol. Disord. 13, 1756286420910310 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hakkarainen, K. M. et al. Pregnancy outcomes after exposure to interferon beta: a register-based cohort study among women with MS in Finland and Sweden. Ther. Adv. Neurol. Disord. 13, 1756286420951072 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Klehmet, J., Begus-Nahrmann, Y., Taipale, K., Niemczyk, G. & Rehberg-Weber, K. Impact of interferon beta exposure on birth outcome and child development – results from the post-authorisation safety study PRIMA. Mult. Scler. Relat. Disord. 77, 104844 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Baechler, E. C. et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc. Natl Acad. Sci. USA 100, 2610–2615 (2003).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bjorkander, S. et al. Pregnancy-associated inflammatory markers are elevated in pregnant women with systemic lupus erythematosus. Cytokine 59, 392–399 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bjorkander, S., Heidari-Hamedani, G., Bremme, K., Gunnarsson, I. & Holmlund, U. Peripheral monocyte expression of the chemokine receptors CCR2, CCR5 and CXCR3 is altered at parturition in healthy women and in women with systemic lupus erythematosus. Scand. J. Immunol. 77, 200–212 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, S. et al. Th1/Th2 associated transcription factors and cytokines in pregnancies with systemic lupus erythematosus. Clin. Exp. Rheumatol. 43, 105–111 (2025).

    PubMed 

    Google Scholar
     

  • Li, H. H. et al. Systemic lupus erythematosus dysregulates the expression of long noncoding RNAs in placentas. Arthritis Res. Ther. 24, 142 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fierro, J. J. et al. Immunohistochemical analysis reveals higher myxovirus resistance protein 1 expression and increased macrophage count in placentas from patients with systemic rheumatic diseases. Rheumatol. Int. 45, 90 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chakravarty, E., Clowse, M. E., Pushparajah, D. S., Mertens, S. & Gordon, C. Family planning and pregnancy issues for women with systemic inflammatory diseases: patient and physician perspectives. BMJ Open. 4, e004081 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Skorpen, C. G. et al. Influence of disease activity and medications on offspring birth weight, pre-eclampsia and preterm birth in systemic lupus erythematosus: a population-based study. Ann. Rheum. Dis. 77, 264–269 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Humbert, M. et al. 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur. Heart J. 43, 3618–3731 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Goldstein, R. F. et al. Association of gestational weight gain with maternal and infant outcomes: a systematic review and meta-analysis. JAMA 317, 2207–2225 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shard, A., Prodger, C. & Pavord, S. Venous thromboembolism still leads on maternal death. Res. Pract. Thromb. Haemost. 9, 102675 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Esposito, G. et al. Parents’ age and total fertility rate in selected high-income countries from Europe and North America, 1990-2020. Eur. J. Obstet. Gynecol. Reprod. Biol. 299, 32–36 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Normand, G. et al. Not only disease activity but also chronic hypertension and overweight are determinants of pregnancy outcomes in patients with systemic lupus erythematosus. Lupus 28, 529–537 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Miyakis, S. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J. Thromb. Haemost. 4, 295–306 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Barbhaiya, M. et al. 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Ann. Rheum. Dis. 82, 1258–1270 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ruiz-Irastorza, G. & Khamashta, M. A. Managing lupus patients during pregnancy. Best. Pract. Res. Clin. Rheumatol. 23, 575–582 (2009).

    Article 
    PubMed 

    Google Scholar
     

  • Schreiber, K. et al. British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: comorbidity medications used in rheumatology practice. Rheumatology 62, e89–e104 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hu, Z., Gao, R., Huang, W., Wang, H. & Qin, L. Effect of hydroxychloroquine on lupus activity, preeclampsia and intrauterine growth restriction in pregnant women with systemic lupus erythematosus and/or antiphospholipid syndrome: a systematic review and meta-analysis. J. Clin. Med. https://doi.org/10.3390/jcm12020485 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Do, S. C., Rizk, N. M., Druzin, M. L. & Simard, J. F. Does hydroxychloroquine protect against preeclampsia and preterm delivery in systemic lupus erythematosus pregnancies? Am. J. Perinatol. 37, 873–880 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Schreiber, K. et al. Global comment on the use of hydroxychloroquine during the periconception period and pregnancy in women with autoimmune diseases. Lancet Rheumatol. 5, e501–e506 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rolnik, D. L. et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N. Engl. J. Med. 377, 613–622 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Roberge, S., Bujold, E. & Nicolaides, K. H. Aspirin for the prevention of preterm and term preeclampsia: systematic review and metaanalysis. Am. J. Obstet. Gynecol. 218, 287–293.e1 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bleau, N., Patenaude, V. & Abenhaim, H. A. Risk of venous thromboembolic events in pregnant patients with autoimmune diseases: a population-based study. Clin. Appl. Thromb. Hemost. 22, 285–291 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Griffin, M. M. et al. Risk assessment model for postpartum venous thromboembolism prevention in patients with systemic lupus erythematosus. Am. J. Perinatol. 40, 1732–1737 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • van Vollenhoven, R. F. et al. 2021 DORIS definition of remission in SLE: final recommendations from an international task force. Lupus Sci. Med. https://doi.org/10.1136/lupus-2021-000538 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Moghib, K. et al. Efficacy of vitamin D supplementation on the incidence of preeclampsia: a systematic review and meta-analysis. BMC Pregnancy Childbirth 24, 852 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bultink, I. E. M. Bone disease in connective tissue disease/systemic lupus erythematosus. Calcif. Tissue Int. 102, 575–591 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hofmeyr, G. J., Lawrie, T. A., Atallah, A. N., Duley, L. & Torloni, M. R. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD001059.pub4 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cluver, C. A., Rohwer, C. & Rohwer, A. C. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst. Rev. 12, CD001059 (2025).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Borges, M. C., Moura dos Santos, F. de M., Telles, R. W., Lanna, C. C. & Correia, M. I. Nutritional status and food intake in patients with systemic lupus erythematosus. Nutrition 28, 1098–1103 (2012).

    Article 
    PubMed 

    Google Scholar
     

  • Pocovi-Gerardino, G. et al. Dietary intake and nutritional status in patients with systemic lupus erythematosus. Endocrinol. Diabetes Nutr. 65, 533–539 (2018).

    Article 

    Google Scholar
     

  • Balevic, S. J. et al. Hydroxychloroquine PK and exposure-response in pregnancies with lupus: the importance of adherence for neonatal outcomes. Lupus Sci. Med. https://doi.org/10.1136/lupus-2021-000602 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schreiber, K. et al. Impact of conflicting information on the use of antirheumatic drugs in pregnancy and breastfeeding: perspectives of healthcare providers from the global PRAISE survey. Ther. Adv. Musculoskelet. Dis. 17, 1759720X251350087 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Simeoni, U., Messer, J., Weisburd, P., Haddad, J. & Willard, D. Neonatal renal dysfunction and intrauterine exposure to prostaglandin synthesis inhibitors. Eur. J. Pediatr. 148, 371–373 (1989).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dong, Y. et al. Risk of gestational diabetes mellitus in systemic lupus erythematosus pregnancy: a systematic review and meta-analysis. BMC Pregnancy Childbirth 19, 179 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pluma, A. et al. Antirheumatic drugs in reproduction, pregnancy, and lactation: a systematic literature review informing the 2024 update of the EULAR recommendations. Ann. Rheum. Dis. 84, 1561–1590 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Giles, I., Yee, C. S. & Gordon, C. Stratifying management of rheumatic disease for pregnancy and breastfeeding. Nat. Rev. Rheumatol. 15, 391–402 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Michael, A. et al. Use of antenatal fluorinated corticosteroids in management of congenital heart block: systematic review and meta-analysis. Eur. J. Obstet. Gynecol. Reprod. Biol. X 4, 100072 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Giles, I. et al. The time of equipoise on the use of biological DMARDs in for inflammatory arthritis during pregnancy is finally over: a reappraisal of evidence to optimise pregnancy management. Lancet Rheumatol. 6, e546–e559 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Siegel, C. H. & Sammaritano, L. R. Biologic disease-modifying antirheumatic drug use during pregnancy and lactation. Obstet. Gynecol. https://doi.org/10.1097/AOG.0000000000006193 (2026).

    Article 
    PubMed 

    Google Scholar
     

  • Lorenzo-Vizcaya, A. & Isenberg, D. A. The use of anti-TNF-alpha therapies for patients with systemic lupus erythematosus. Where are we now? Expert. Opin. Biol. Ther. 21, 639–647 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kao, J. H. et al. Pregnancy outcomes in patients treated with belimumab: report from real-world experience. Semin. Arthritis Rheum. 51, 963–968 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Chakravarty, E. F., Murray, E. R., Kelman, A. & Farmer, P. Pregnancy outcomes after maternal exposure to rituximab. Blood 117, 1499–1506 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Klink, D. T., van Elburg, R. M., Schreurs, M. W. & van Well, G. T. Rituximab administration in third trimester of pregnancy suppresses neonatal B-cell development. Clin. Dev. Immunol. 2008, 271363 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Victora, C. G. et al. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet 387, 475–490 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Acevedo, M., Pretini, J., Micelli, M., Sequeira, G. & Kerzberg, E. Breastfeeding initiation, duration, and reasons for weaning in patients with systemic lupus erythematosus. Rheumatol. Int. 37, 1183–1186 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Li, W. & Wang, T. Breastfeeding initiation, duration, and associated factors in mothers with systemic lupus erythematosus. Breastfeed. Med. 17, 958–963 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lieber, S. B. et al. Infant feeding experiences of women with systemic lupus erythematosus: a qualitative study. Lupus 34, 365–373 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Berwick, M. A. P., Heuberger, A. J., Martin, J. V., Hale, T. W. & Louis-Jacques, A. F. Drugs in Lactation. Semin. Perinatol. 49, 152077 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Datta, P., Baker, T. & Hale, T. W. Balancing the use of medications while maintaining breastfeeding. Clin. Perinatol. 46, 367–382 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Verstegen, R. H. J. & Ito, S. Drugs in lactation. J. Obstet. Gynaecol. Res. 45, 522–531 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Lien, H. J. T. et al. Single-cell resolution of longitudinal blood transcriptome profiles in rheumatoid arthritis, systemic lupus erythematosus and healthy control pregnancies. Ann. Rheum. Dis. 83, 300–311 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schreiber, K. et al. Challenges of designing and conducting cohort studies and clinical trials in populations of pregnant people. Lancet Rheumatol. 6, e560–e572 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar